Controlled Release Ammonio Methacrylate Copolymer-Based Microspheres of Oxypentifylline
Keywords:
Oxypentifylline, Ammonio Methacrylate Copolymer RS100, Microspheres, Sustained release, Entrapment efficiencyAbstract
The objective of this work was to formulate and evaluate a controlled-release Oxypentifylline microspheres that fulfill the requirements for extended release medications using Ammonio Methacrylate Copolymer RS100 as polymeric material. The microsphere were prepared by quasiemulsion solvent diffusion technique. The effect of process variables such as drug to polymer ratio, stirring rate, and concentration of emulsifier on mean particle size, yield, entrapment efficiency and in vitro release characteristics of microspheres were studied. The prepared microspheres were spherical in shape. The size range varied from 325.45 to 518.54 µm. The microspheres showed high entrapment efficiency (94.22%) and the release was extended up to 24 hrs. The best microsphere formulation was selected and subjected for in vivo studies which reveal that the bioavailability of the drug increased by more than 3.4 times by formulating it into microspheres. This study indicated that Ammonio Methacrylate Copolymer RS 100 can use successfully to sustain the release of Oxypentifylline
References
. Ward A, Clissold SP. Pentoxifylline. A
review of its pharmacodynamic and
pharmacokinetic properties, and its
therapeutic efficacy. Drugs.;34 (1987)
–97.
. Eun BL, Liu XH, Barks JD.
Pentoxifylline attenuates hypoxicischemic brain injury in immature rats.
Pediatr Res;47.(2000)73–78.
. Muller R. Hemorheology and
peripheral vascular diseases: A new
therapeutic approach. J
Med.;12(1981)209–35.
. Gunawan I., Achmad S.,
Moegihardjo, Soeharyono, Tjiang L.,
Iis W., Lisa A., Harry G. B.
Pentoxifylline. Analytical Profiles of
Drug Substances and Excipients
(1998)295-339
. Samlaska CP, Winfield EA.
Pentoxifylline. J Am Acad
Dermatol..30(1994)603–21.
. Hardman J.G., L.E. Limbird, A.G.
Gilman: The pharmacological basis of
therapeutics,. 8th ed., Vol. II., New
York: Maxwell Macmillan Publishing
Corporation: 1699. (1992)
. Grigoleith.G., H. Lleonhardit Rheology
of blood and pentoxifylline,
Pharmatherapeutica, 1, 10 (1997) 642
– 651
. Popovici I., D. Lupuliasa: Tehnologie
farmaceutică, vol. I, Editura Polirom
Iaşi: (1997)25 – 37
. Sudhamani, T., Reddy, K. N., Kumar,
V. R. R., Revathi, R. and Ganesan, V.:
preparation and evaluation of ethyl
cellulose microspheres of ibuprofen
for sustained drug delivery. Int. J.
Pharm. Res. Dev. 2(8) (2010)119-125.
. Deore, B.V., Mahajan, H. S. and
Deore U.V.: Development and
characterization of sustained release
microspheres by quasi emulsion
solvent diffusion method. Int. J.
ChemTech. Res. 1(3): (2009)634-642.
. Vyas, S. P and Khar, R. K.: Targeted
and controlled drug delivery- Novel
carrier systems, 1st edition, CBS
publishers & distributers, Delhi, (2006)
-458.
. Karal-Yılmaz, O., Serhatl, M., Baysal,
K. and Baysal, B. M.: Preparation and
in vitro characterization of vascular
endothelial growth factor (VEGF)-
loaded poly(D,L-lactic-co-glycolic acid)
microspheres using a double
emulsion/solvent evaporation
technique. J. Microencapsul. 28(1):
(2011) 46-54.
. El-Bagory, I. M., Hosny, E. A., AlSuwayeh, S. A., Mahrous, G. M. and
Al-Jenoobi, F. I.: Effects of sphere
size, polymer to drug ratio and
plasticizer concentration on the
release of theophylline from
ethylcellulose microspheres. Saudi
Pharm. J. 15(3-4): (2007) 213-217.
. Liu, H., Pan, W., Ke, P., Dong, Y. and
Ji, L.: Preparation and evaluation of a
novel gastric mucoadhesive
sustained-release acyclovir
microsphere. Drug. Dev. Ind. Pharm.
(9): (2010)1098-1105.
. Huh, Y., Cho, H. J., Yoon, I. S., Choi,
M. K. Kim, J. S., Oh, E., Chung, S. J.,
Shim, C. K. and Kim, D. D.:
Preparation and evaluation of spraydried hyaluronic acid microspheres for
intranasal delivery of fexofenadine
hydrochloride. Eur. J. Pharm. Sci.
(1): (2010)9-15.
. Rassu, G., Gavini, E., Spada, G.,
Giunchedi, P. and Marceddu, S.
pentoxiphylline spray-dried
microspheres based on [AM
Polymer]RS and RL: study of the
manufacturing parameters. Drug. Dev.
Ind. Pharm. 34(11): (2008) 1178-1187.
. Kibbe, A. H.. Handbook of
pharmaceutical excipients. 3rd edn.
Washington, D.C., USA, American
Pharmaceutical Association,
(2000)401-406.
. Apu, A. S., Pathan, A. H., Shrestha,
D., Kibria, G. and Jalil, J.:
Investigation of In vitro Release
Kinetics of Carbamazepine from
Ammonio Methacrylate Copolymer®
RS PO and RL PO Matrix Tablets.
Trop. J. Pharm. Res. 8 (2): (2009)
-152.
. Kawashima Y., Iwamoto T., Niwa T.,
Takeuchi H., Hino T.: J.
Microencapsul. 10, (1993) 329.
. Nocent M., Bertochhhi L., Espitalier F.,
Baron B., Couarraze G.: J. Pharm.
Sci. 90, (2001) 1620.
. Sato Y., Kawashima Y., Taceuchi H.,
Yamamoto H.: Eur. J. Pharm.
Biopharm. 20, 1(2003).
. Devrim B, Canefe K. Preparation and
evaluation of modified release
ibuprofen microspheres with acrylic
polymers (eudragit) by quasi emulsion
Solvent diffusion method: effect of
variables. Acta Poloniae
Pharmaceutica & Drug Res.;
(2006)521-534.
. Trivedi, P., Verma, A. M. L. and
Garud, N. : Preparation and
characterization of aceclofenac
microspheres. Asian J. Pharm.
(2008)110-115.
. Ansel, H. C., Popovich, N. G. and
Allen, J. R.: In Pharmaceutical dosage
forms and drug delivery systems. 6th
ed. Williams and Wilkins. London.
(1995)P: 175.
. Behera, B. C., Sao, S. K., Dhal, S.,
Baric, B. B. and Gupta, B. K.:
Characterization of Glipizide-Loaded
Polymethacrylate Microspheres
Prepared By an Emulsion Solvent
Evaporation Method. Trop. J. Pharm.
Res. 7 (1): (2008) 879-885.
. Chinna B, Shyam R., Vimal M., Sleeva
M., Sai M. Formulation and Evaluation
of Indomethacin Microspheres using
natural and synthetic polymers as
Controlled Release Dosage Forms.
International Journal of Drug
Discovery, 2(1), (2010)8-16
. Anita V., Akanksha T., Shubhini A. ,
Shailendra S. Fabrication and
evaluation of sustained release
microsphere of ketorolac
tromethamine. International Journal of
Pharmacy and Pharmaceutical
Sciences. 2(4), 2010
. Valliappan, K., Kannan, K.,
Sivakumar, T. and Manavalan, R.:
Enantiospecific pharmacokinetic
studies on pentoxiphylline in tablet
formulation using indirect chiral HPLC
analysis. J. Appl. Biomed. 4: (2006)
–161.
. Robert V. Smith, Shun K., Patrick
J. Davis, Michael T. Bauza.
Determination of pentoxifylline and its
major metabolites in microbial extracts
by thin-layer and high-performance
liquid chromatography. Journal of
Chromatography (1983) 281-287
. Meyyanathan, S. N., Muralidharan, S.,
Rajan, S., Gopal, K. and Suresh, B.: A
Simple Sample Preparation with
HPLC–UV Method for Estimation of
Amlodipine from Plasma: Application
to Bioequivalence Study. The Open
Chem. Biomed. Meth. J. 1: (2008) 22-
. Chaisri, C., Hennink, W. E. and
Okonogi, S.: Preparation and
characterization of cephalexin loaded
PLGA microspheres. Cur. Drug Deliv.
(2009) 69-75.
. Parashar, V., Ahmad, D., Gupta, S. P.,
Upmanyu, N., Parashar, N. and
Mudgal, V.: Formulation and
evaluation of biodegradable
microspheres of tinidazole. Int. J. Drug
Deliv. 2 (2010) 238-241.
. Mostafa S., Malihe S., Mehdi S.,
Formulation and in vitro Evaluation of
Eudragit L100 Microspheres of
piroxicam Nature Precedings :
(2008)27
. Maia, J. L., Santana, M. H. A. and Re,
M. I.: The effect of some processing
conditions on the characteristics of
biodegradable microspheres obtained
by an emulsion solvent evaporation
process. Braz. J. Chem. Eng.
(2004) 1-12.
. Mazumder, B., Dey, S., Bhattacharya,
S., Sarkar, S. and Mohanta, B.:
Formulation and cheracterization of
cellulose-based microspheres of
chlorpheniramine maleate. Arch.
Pharm. Sci. 1 (1) (2009) 66-74.
. Lin, S. Y., Tzan, Y. L., Lee, C. J. and
Weng, C. N.: Preparation of entericcoated microspheres of mycoplasma
hypneumoniae vaccine with cellulose
acetate phethalate (I) formation
condition and micrometric properties.
J. Microencapsul. 8(3) (1991) 317-
. Mao, S., Shi, y., Li, L. Xu, J., Schaper,
A. and Kissel, T. : Effect of process
and formulation parameters on
characteristics and internal
morphology of poly (D, L-lactide-coglycolide) microspheres formed by the
solvent evaporation method. Eur. J.
Pharm. Biopharm. 68 (2008) 214-223.
. Gupta, B. K., Pal, R., Chakraborty, M.
and Debnath, R.: Design, evaluation
and optimization of microcapsules of
leflunomide with [AM Polymer]RL100
and [AM Polymer]RS100 by solvent
evaporation technique. Asian J.
Pharm. 3 (4) (2009)309-313.
. Prasanth, V. V, Chakraborty, A.,
Mathew, S.T., Mathappan, R. and
Kamalakkannan, V.: Formulation and
evaluation of Salbutamol sulphate
microspheres by solvent evaporation
method. J. of Appl. Pharm. Sci. 1 (5)
(2011) 133-137.
. Mateeovic T, Kriznar B, Bogataj M,
Mrhar A. The influence of stirring rate
on biopharmaceutical properties of
Eudragit RS microspheres. J
Microencapsul. 19 (2005) 29‐36.
. Pachuau, L. and Mazumder, B.: study
on the effects of different surfactants
on Ethylcellulose microspheres. Int. J.
Pharm. Tech. Res. 1(4) (2009) 966-
. Cui, F., Yang, M., Jiang, Y., Cun, D.,
Lin, W., Fan, Y. and Kawashima, Y.:
Design of sustained-release
nitrendipine microspheres having solid
dispersion structure by quasi-emulsion
solvent diffusion method. J. Control.
Rel. 91(2003) 375–384.